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or such effect, suggesting helix G as a possible target for aromatase inhibition. Aneuploidy is the most frequent cause of early-embryo abortion. Any defect in chromosome segregation would fail to satisfy the spindle assembly checkpoint (SAC) during mitosis, halting metaphase and causing aneuploidy. The mitotic checkpoint complex (MCC), comprising MAD1, MAD2, Cdc20, BUBR1 and BUB3, plays a vital role in SAC activation. Studies have confirmed that overexpression of MAD2 and BUBR1 can facilitate correct chromosome segregation and embryo stability. Research also proves that miR-125b negatively regulates MAD1 expression by binding to its 3'UTR. However, miR-125b, Mad1 and Bub3 gene expression in aneuploid embryos of spontaneous abortion has not been reported to date. In this study, embryonic villi from miscarried pregnancies were collected and divided into two groups (aneuploidy and euploidy) based on High-throughput ligation-dependent probe amplification (HLPA) and Fluorescence in situ hybridization (FISH) analyses. RNA levels of miR-125b, MAD1 and BUB3 were detected by Quantitative real-s first confirmed the negative regulatory mode between MAD1 and miR-125b, providing a basis for further mechanism researches in aneuploid abortion. Retinoids are promising agents in the treatment of different types of neoplasia including estrogen receptor-positive breast cancers, whereas refractoriness/low sensitivity is observed in triple-negative breast cancer (TNBC) subtype. However, the reason for these diverse retinoid-sensitivity remains elusive. Determinants of retinoid sensitivity were investigated using immunohistochemistry of primary patient samples, and identified retinoic acid receptor α (RARα) as a putative factor. The anti-tumor activity of hypo-phosphorylated RARα was investigated in TNBC cell models and a xenograft mouse model. Next, miRNA sequencing analysis was performed to identify the target miRNA of RARα, and luciferase reporter was used to confirm the direct target gene of miR-3074-5p. We discovered that serine-77 residue of RARα was constantly phosphorylated, which correlated with TNBC's resistance to retinoids. Overexpression of a phosphorylation-defective mutant RARαS77A mimicked activated RARα and repressed TNBC cell progression both in vitro and in vivo, via activating cell cycle arrest, apoptosis, and cytotoxic autophagy, independent of RARα agonists. https://www.selleckchem.com/products/azd0156-azd-0156.html We further revealed that the anti-tumor action of RARαS77A was, at least in part, mediated by the up-regulation of miR-3074-5p, which directly targeted DHRS3, a reductase negatively associated with TNBC patient survival. Our results suggest that the inhibition of RARαS77 phosphorylation by either expressing RARαS77A or inhibiting RARα's phosphokinase CDK7, can bypass RA stimuli to transactivate tumor-suppressive miR-3074-5p and reduce oncogenic DHRS3, thus overcoming the RA-resistance of TNBC. The novel regulatory network, involving RARαS77 phosphorylation, miR-3074-5p, and DHRS3, emerges as a new target for TNBC treatment. The novel regulatory network, involving RARαS77 phosphorylation, miR-3074-5p, and DHRS3, emerges as a new target for TNBC treatment. Moving evidence-based practices into the hands of practitioners requires the synthesis and translation of research literature. However, the growing pace of scientific publications across disciplines makes it increasingly difficult to stay abreast of research literature. Natural language processing (NLP) methods are emerging as a valuable strategy for conducting content analyses of academic literature. We sought to apply NLP to identify publication trends in the journal Implementation Science, including key topic clusters and the distribution of topics over time. A parallel study objective was to demonstrate how NLP can be used in research synthesis. We examined 1711 Implementation Science abstracts published from February 22, 2006, to October 1, 2020. We retrieved the study data using PubMed's Application Programming Interface (API) to assemble a database. Following standard preprocessing steps, we use topic modeling with Latent Dirichlet allocation (LDA) to cluster the abstracts following a minimization studies to expand the impact of implementation science on disadvantaged communities. We demonstrated how NLP can be used as a synthesis and translation method to identify trends and topics across a large number of (over 1700) articles. With applicability to a variety of research domains, NLP is a promising approach to accelerate the dissemination and uptake of research literature. For future research in implementation science, we encourage the inclusion of more equity-focused studies to expand the impact of implementation science on disadvantaged communities. Regular supervision of patients with type-2 diabetes mellitus (T2DM) by healthcare providers is essential to optimise their glycaemic control but is challenging to achieve in current care models. Telemonitoring is postulated to bridge this gap by leveraging on internet-of-things and mobile-health technology. This study aims to determine the effectiveness of a novel telemonitoring system (OPTIMUM) in improving the glycaemic control of patients with T2DM compared with standard of care alone. This mixed-method study comprises an initial randomised controlled trial involving 330 Asian adults with T2DM, aged 26-65 years old with an HbA1c of 7.5-10%, with 115 in the intervention and control arms each. Those in the intervention arm will use standardised Bluetooth-enabled devices to transmit their capillary glucose, blood pressure and weight measurements to the OPTIMUM system. Primary care physicians and nurses will remotely supervise them according to an embedded management algorithm for 6 months, including telestandard of care. The results of this trial will better inform policy makers in adopting telemedicine for population health management. ClinicalTrials.gov NCT04306770 . Registered on March 13, 2020. ClinicalTrials.gov NCT04306770 . Registered on March 13, 2020. Plantar heel pain (PHP) accounts for 11-15% of foot symptoms requiring professional care in adults. Recovery is variable, with no robust prognostic guides for sufferers, clinicians or researchers. Therefore, we aimed to determine the validity, reliability and feasibility of questionnaire, clinical and biomechanical measures selected to generate a prognostic model in a subsequent cohort study. Thirty-six people (19 females & 17 males; 20-63 years) were recruited with equal numbers in each of three groups people with PHP (PwPHP), other foot pain (PwOP) and healthy (H) controls. Eighteen people performed a questionnaire battery twice in a randomised order to determine online and face-to-face agreement. The remaining 18 completed the online questionnaire once, plus clinical measurements including strength and range of motion, mid-foot mobility, palpation and ultrasound assessment of plantar fascia. Nine of the same people underwent biomechanical assessment in the form of a graded loaded challenge augmenting walking with added external weight and amended step length on two occasions.
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